Evidence map›Paper›PMID 23823219›Full record

ArticleBiophysical journal2013

Nonlinear strain stiffening is not sufficient to explain how far cells can feel on fibrous protein gels.

Mathilda S Rudnicki, Heather A Cirka, Maziar Aghvami, Edward A Sander, Qi Wen, Kristen L Billiar

Open access · bronzeAbstract read
In one paragraph

Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 119 citations in OpenAlex.

  1. Article
  2. Cyclic stretch inhibits cell invasion in 3D scaffolds.bioRxiv : the preprint server for biology · 2026
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  11. Effect of hyaluronic acid on microscale deformations of collagen gels.Journal of the mechanical behavior of biomedical materials · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Mathilda S RudnickiDepartment of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts, USA.
Heather A Cirka
Maziar Aghvami
Edward A Sander
Qi Wen
Kristen L Billiar
Worcester Polytechnic Institute · USUniversity of Iowa · US

Funding

Regulation of valvular interstitial cell fate: Role of boundary stiffnessR15HL087257 · NHLBI · WORCESTER POLYTECHNIC INSTITUTE · PI BILLIAR, KRISTEN L · 2009 to 2017
$681k
NHLBI NIH HHS 1R15HL087257-01A2NHLBI NIH HHS R15 HL087257
6 · The paper itself

Abstract

Recent observations suggest that cells on fibrous extracellular matrix materials sense mechanical signals over much larger distances than they do on linearly elastic synthetic materials. In this work, we systematically investigate the distance fibroblasts can sense a rigid boundary through fibrous gels by quantifying the spread areas of human lung fibroblasts and 3T3 fibroblasts cultured on sloped collagen and fibrin gels. The cell areas gradually decrease as gel thickness increases from 0 to 150 μm, with characteristic sensing distances of >65 μm below fibrin and collagen gels, and spreading affected on gels as thick as 150 μm. These results demonstrate that fibroblasts sense deeper into collagen and fibrin gels than they do into polyacrylamide gels, with the latter exhibiting characteristic sensing distances of <5 μm. We apply finite-element analysis to explore the role of strain stiffening, a characteristic mechanical property of collagen and fibrin that is not observed in polyacrylamide, in facilitating mechanosensing over long distances. Our analysis shows that the effective stiffness of both linear and nonlinear materials sharply increases once the thickness is reduced below 5 μm, with only a slight enhancement in sensitivity to depth for the nonlinear material at very low thickness and high applied traction. Multiscale simulations with a simplified geometry predict changes in fiber alignment deep into the gel and a large increase in effective stiffness with a decrease in substrate thickness that is not predicted by nonlinear elasticity. These results suggest that the observed cell-spreading response to gel thickness is not explained by the nonlinear strain-stiffening behavior of the material alone and is likely due to the fibrous nature of the proteins.

Indexed as

Nonlinear DynamicsStress, MechanicalCollagenElasticityFibrinFibroblastsFinite Element AnalysisGelsHumansCollagenFibrinGels

Identifiers

PMID23823219
PMCPMC3699756
OpenAlexW2008652184

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.